Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS): Key and integrated findings

Between 2019 and 2023, we observed a plateau in the quantity of medically important antimicrobials sold for use in animals. Meanwhile, the median quantity of antimicrobials sold for use in production animals continued to decrease annually across 31 European network countries. As a result, our ranking of antimicrobial sales, compared to Europe, is worsening. From our volunteer sentinel farm surveillance, between 2019 and 2023, we observed a decreasing trend in antimicrobial use (AMU) on broiler chicken, turkey, and grower-finisher pig farms and on beef cattle feedlots. For sentinel dairy cattle farms, AMU increased between 2019 and 2022, which may be partially attributed to improved reporting in 2021 and 2022. Data from Fisheries and Oceans Canada showed a decrease in AMU for aquaculture operations between 2019 and 2022, with an increase between 2021 and 2022. Less than 2% of reported AMU (defined daily doses per 1,000 animal-days at risk) on sentinel terrestrial farms were Category I antimicrobials (considered of very high importance in human medicine).

At the same time, we are seeing increases in concerning resistances. There are increases in extended-spectrum beta-lactamase-producing non-typhoidal Salmonella across humans, animals and food. There are increases in the percentage of ciprofloxacin resistance in Campylobacter in animals and food, along with increases in the quantity of fluoroquinolones sold for use in animals. For people, the trend in percentages of ciprofloxacin resistance in Campylobacter was variable, however, the overall percentage was high (≥30%) or very high (≥60%) depending on the Campylobacter species and year. At the same time, the quantity of fluoroquinolones used in people has decreased. With respect to mobile colistin resistance (mcr), in 2023, we detected mcr genes in a human Salmonella isolate and an Aeromonas isolate from imported shrimp. Nalidixic acid resistance in Salmonella Enteritidis from poultry continued to increase, as well as gentamicin resistance in Campylobacter from feedlot cattle. The quantity of third generation cephalosporins sold for use in animals increased, however, ceftriaxone resistance in E. coli and non-typhoidal Salmonella from animals and food remained stable. For feedlot cattle, the frequency of streptogramin resistance in Enterococcus increased, mirrored by an increase in the reported use of streptogramins in-feed.

As CIPARS continues to work towards embracing a One Health approach, we have new information on AMR in select bacteria from water, farm environments, feed ingredients and mixed feed intended for animals and additional retail commodities. Resistance to Category I antimicrobials was found in isolates from both surface water and the environment of sick animals. Resistant non-typhoidal Salmonella from serovars that can cause disease in Canadians were found in feed ingredients and mixed feeds intended for animals. CIPARS has also partnered with AMRNet-Vet to look at AMR in animal pathogens from samples sent to veterinary diagnostic laboratories, starting with pathogens causing bovine respiratory disease. This complements our work with surveillance of healthy feedlot cattle for the same respiratory pathogens. Over the past five years, we have found that there is less resistance when cattle arrive at the feedlot, yet during the same time, resistance at the time of cattle re-handling has increased (including multidrug resistance).

Other advancements in surveillance activities include antimicrobial sales data by province/region using a biomass denominator and the inclusion of data on dispensing of antimicrobials from community pharmacies for use in companion animals, which includes small amounts of carbapenems.

Ceftriaxone-resistance in non-typhoidal Salmonella, S. Heidelberg, S. Kentucky, and E. coli from chicken(s) and/or people, and ceftiofur use in broiler chicken flocks.

Importance: Third generation cephalosporins are considered of very high importance to human medicine¹ in Canada and around the world². While salmonellosis is often not treated in people, if treatment is needed, third generation cephalosporins are one of the only treatment options for children and pregnant women³. Salmonella Heidelberg is a serovar (i.e., a strain of Salmonella) that tends to make people very sick^3,4.

Data to action: Historically, in Canada, Salmonella Heidelberg was one of the most commonly reported third-generation cephalosporin-resistant Salmonella serovars recovered from poultry and people⁵. A third-generation cephalosporin (ceftiofur) was used in chickens to prevent E. coli omphalitis⁵.

Following a voluntary withdrawal of ceftiofur for use in disease prevention by the poultry industry in 2005 and then again in 2014, there was a reduction in the frequency of ceftriaxone resistance in Salmonella from broiler chickens (both healthy chickens on farm and at slaughter, sick chickens (clinical cases)) and in chicken purchased at the grocery store (Figure 1). Importantly, there was also a reduction in ceftriaxone-resistant S. Heidelberg in people (Figure 1).

In chicken(s), this trend was also observed in E. coli (Figure 1) adding further evidence to a common selective pressure for the resistant determinant. Over time, we also observed an increase in ceftriaxone resistance in S. Kentucky (Figure 1), which is a serovar we see in chickens, but rarely in people in Canada.

Ceftriaxone-resistant S. Heidelberg has not been found in healthy broiler chicken on farm since 2018. From 2003 to 2019, S. Heidelberg was a top 3 serovar from humans composing 6 to 21% of human Salmonella isolates. However, in 2023 in humans, S. Heidelberg contributed to less than 1% of isolates and was not in the top 10 serovars.

Figure 1. CIPARS-FNC: Frequency of ceftriaxone resistance in non-typhoidal Salmonella and Escherichia coli isolates from chicken(s) and/or people, and ceftiofur use in broiler chicken flocks.

Hover over the line or bar graph to see more details. Click on a legend element to add or remove the corresponding lines from the graph. Red text in the hover over field highlights a small total isolate count (less than 20).

Increasing frequency of ESBL-producing non-typhoidal Salmonella from humans, animals and food.

Importance: Extended-spectrum β-lactamase (ESBL)-producing Salmonella are resistant to third-generation cephalosporins. Salmonella are part of the Enterobacterales order. ESBL-producing Enterobacterales are in the ‘Tier 1: High-priority’ group of antimicrobial-resistant pathogens of concern in Canada¹ and a critical group according to the World Health Organization’s Bacterial Priority Pathogens List, 2024².

What the data are telling us: ESBL-producing non-typhoidal Salmonella (NTS) from humans and animal/food sources continues to steadily increase (Figure 1). Of all the Salmonella tested, the frequency of ESBL-producing Salmonella prior to 2017 was 0.5% for humans (n = 27 ESBL isolates / 5010 total NTS isolates) and 0.1% for animals and food (n = 2 / 2086). Whereas in 2023, the frequencies rose to 1.6% (n = 91 / 5843) and 1.7% (n = 36 / 2113), respectively (Figure 1).

In humans, of all ESBLs, the predominant ESBL gene (bla_CTX-M-65) decreased from 66% in 2019 to 42% in 2023 and the majority were found in S. Infantis (n = 33). Whereas the second most predominant ESBL gene, bla_CTX-M-55, increased from 13% in 2019 to 37% in 2023. The majority of these bla_CTX-M-55 carrying isolates were Salmonella I 4,[5],12:i:- (n = 22).

In animals and food, of all ESBL carrying isolates, the predominant ESBL gene was bla_CTX-M-65, which increased from 24% in 2018, to 59% in 2022 to 80% in 2023. In 2023, the majority of these bla_CTX-M-65 carrying isolates were S. Infantis (n = 21).

Figure 1. CIPARS-FNC: Frequency of ESBL-producing non-typhoidal Salmonella from humans, animals and food.

Hover over the line or bar graph to see more details. Click on a legend element to add or remove the corresponding lines from the graph.

Nalidixic acid resistance in Salmonella Enteritidis from chicken(s)

Importance: Salmonella Enteritidis isolates from chickens and chicken meat were historically almost 100% susceptible to all the antimicrobials that CIPARS tested. However, in 2018 CIPARS reported the emergence of nalidixic acid-resistant S. Enteritidis from chicken(s). Nalidixic acid is a quinolone and resistance to quinolones can often be a precursor to resistance to fluoroquinolones. These isolates with nalidixic acid resistance also had reduced susceptibility to fluoroquinolones. Fluoroquinolones are considered of very high importance to human medicine¹ in Canada and around the world².

Salmonella Enteritidis is one of the top serovars that we find in people with salmonellosis and one of the top serovars we see in chicken(s). with salmonellosis and one of the top serovars we see in chicken(s).

What the data are telling us: In 2018, nalidixic acid resistance in S. Enteritidis was first detected in CIPARS isolates (n = 5 isolates) from healthy chickens at slaughter, sick chickens (clinical cases) and chicken meat (Figure 1). These proportions were mostly stable until 2022 when CIPARS observed a substantial spike in resistance across farm, abattoir, retail, and diagnostic chicken isolates (Figure 1). In 2023, nalidixic acid resistance was found in the following components/sources: chicken meat (n = 21 resistant isolates / 70 total S. Enteritidis isolates), diagnostic samples from sick chickens (n = 31 / 78), healthy chicken at slaughter (n = 6 / 31) and healthy broiler chickens on farm (n = 10 / 29) (Figure 1).

This spike in resistance appears to be driven by a GyrA (D87Y) substitution. Further genomic analyses are on-going, including looking at the genes in the human S. Enteritidis isolates.

Figure 1: CIPARS-FNC: Frequency of nalidixic acid resistance in Salmonella Enteritidis from chicken(s)

Hover over the line graph to see more details. Click on a legend element to add or remove the corresponding lines from the graph. Red text in the hover over field highlights a small total isolate count (less than 20).

Ciprofloxacin resistance in Campylobacter and fluoroquinolones sold for use in animals and people.

Importance: CIPARS has been watching an increasing trend in ciprofloxacin resistance in Campylobacter across multiple animal species and at different stages along the food chain. Ciprofloxacin is a fluoroquinolone. Fluoroquinolones are considered of very high importance to human medicine¹ in Canada and around the world².

What the data are telling us: Between 2022 and 2023, an increase in ciprofloxacin resistance was observed in Campylobacter recovered from all terrestrial food animal species under surveillance at the farm-level (broiler chickens, laying hensⁱ, turkeys, pigs, dairy cattle and feedlot cattle). Across the food animal species (farm-level), the magnitude of the increase (percentage difference) during this time frame was between 2% and 20%, with high frequencies of ciprofloxacin resistance in 2023 ranging between 19% and 46%. Further genomic analyses are on-going to understand this trend across multiple host species.

Overall, ciprofloxacin resistance in Campylobacter from humans has remained stable, based on data available up to 2022. In C. jejuni, resistance levels were high in 2018 and 2022 (32% and 30%, respectively), although there was a decreasing trend between 2019 (45%) to 2022 (30%). In C. coliⁱⁱ, ciprofloxacin resistance was 70% in 2018 and 60% in 2022, but there was an increasing trend between 2020 (33%) and 2022 (60%).

In 2023, more fluoroquinolones were sold (or intended for use) in humansⁱⁱⁱ than animals (human range: 4.16 to 5.60 mg/kg biomass vs. animal range: 0.04 to 0.11 mg/kg biomass). Between 2019 and 2023, the quantity of fluoroquinolones intended for use in humans decreased by 26% (5.60 to 4.16 mg/kg biomass). Whereas in animals, the quantity of fluoroquinolones sold by manufacturers and importers, while small relative to other antimicrobial classes, increased by 38% (0.08 to 0.11 mg/kg biomass^iv).

Figure 1. CIPARS-FNC: Frequency of ciprofloxacin-resistance in Campylobacter from humans, animals and food

Hover over the line graph to see more details. Click on a legend element to add or remove the corresponding lines from the graph. Red text in the hover over field highlights a small total isolate count (less than 20).